Endocrine therapy with or without radical prostatectomy for T1b-T3N0M0 prostate cancer

BACKGROUND: We retrospectively compared the 5-year survival rates of T1b-T3N0M0 prostate cancer patients treated either by endocrine therapy plus radical prostatectomy or endocrine therapy alone. METHODS: Clinical T1b-T3N0M0 prostate cancer patients were enrolled at 104 institutions in Japan. They were assigned to study 1 (n = 176), if they were indicated to prostatectomy, if not indicated, they were assigned to study 2 (n = 151). The indication of prostatectomy was based on the clinical judgement of physicians and/or patients. Those assigned to study 1 underwent prostatectomy and adjuvant endocrine therapy with or without preoperative androgen deprivation. Those assigned to study 2 were treated with leuprorelin acetate with or without chlormadinone acetate. They were followed-up every 3 months until death or for 5 years and over. RESULTS: Those assigned to study 1 were younger (mean age 67.2 vs 75.7 years), less advanced in clinical stage, and had lower prostate specific antigen levels (mean 43.8 vs 103.6 ng/mL). Death for any reason was observed less frequently in study 1 (n = 29, 16%) than study 2 (n = 50, 33%), and the 5-year overall survival rate was higher in study 1 (87 vs. 68%). However, prostate cancer deaths were comparatively seldom (9% in study 1 and 7% in study 2), resulting in the identical 5-year cause specific survival rate in both study groups (91%). In both study groups the overall survival was almost equal to the natural survival of age-matched men. CONCLUSIONS: Endocrine therapy offers a reasonable survival rate in T1b-T3 prostate cancer patients within a 5-year follow-up. Observation will be extended to determine 10-year outcomes.     

Abnormal cardiac histology in severe intrauterine growth retardation infants

Four infants with severe intrauterine growth retardation (IUGR) weighing less than 1000 g at birth developed heart failure and died in our unit, where heart failure of IUGR infants is the main reason of death in extremely low birth-weight infants. The causes of their heart failure are one of the main themes in current neonatal medicine. The subjects of this study were four small for gestational age infants; all died due to heart failure 5 to 10 days after birth. Microscopic specimens of hearts from autopsies were evaluated with respect to the following characteristics: thickness of myocardial fibers, maturation of nuclei, presence of dysgenesis or necrosis in myocardium, and amount of glycogen in the heart. Neither dysgenesis nor infarction of the heart was found but hypoplasia in myocardial fibers and decreased glycogen levels were observed. Maturation delay in myocytes' nuclei did not appear to be severe. We conclude that these infants' hearts failed to adapt to postnatal hemodynamic changes because of inadequate myocardial function and inadequate glycogen reserves.     

The Acute and Chronic Toxicities of Nivalenol in Mice

The Acute and Chronic Toxicities of Nivalenol in Mice. Ryu,J.-C, Ohtsubo, K., Izumiy-ama, N., Nakamura, JL, Tanaka, T.,Yamamura, H., and Ueno, Y. (1988). Fundam. Appl Toxicol. 11,38–47. In an attempt to ascertain precisely the toxiceffects of nivalenol (N1V), we conducted the determination ofLD50 values, and interim kills during the carcinogenic studyin mice. LD50 values (mg/kg) of NIV in 6-week-old male ddY micewere determined as 38.9 (po), 7.4 (ip), 7.2 (sc), and 7.3 (iv).Seven-week-old female C57BL/6CrSlc SPF mice were fed diets containing0, 6, 12, and 30 ppm (mg/kg) NIV over 1 year, and were assessedfor effects on body weight gain, feed efficiency, terminai organweights, hematology, and histopathology. The rates of body weightgain and feed efficiency showed a good dose-dependent correlationin all experimental periods. Gross and histopathological evaluationof the liver, thymus, spleen, kidneys, stomach, adrenal glands,pituitary gland, ovaries, sternum, bone marrow, lymph node,brain, and small intestines with or without Peyer's patch portionfrom control and all NIV-exposed mice revealed that these tissueswere normal in appearance and in histopathological structure.Also, no changes were observed in the ultrastructural studieson the bone marrow. Dietary NIV did, however, cause dose-dependentdecreases of absolute organ weights (mg) and increases of relativeorgan weights (mg/g body weight) in the terminal organ weightsrecorded. A significant leukopenia was observed in the 30 ppmgroup at 6 months and in all NIV-treated groups at 1 year. Nomarked changes were observed in the other hematological parameters.These results indicated that 6 ppm or more of dietary NIV for1 year showed a characteristic toxic effect of trichothecenemycotoxins in mice.     

Role of vagotony in sinus node dysfunction in children with symptomatic congenital long QT syndrome

The present study examined chronotropic dysfunction and the role of vagotony in congenital long QT syndrome, sinus node function and the effects of parasympathetic blockade. Six patients with congenital long QT syndrome were studied. The four males and two females, aged 1–15 years, had episodes of syncope and malignant ventricular arrhythmias. Congenital long QT syndrome was defined as a corrected QT interval greater than 0.45 s, T wave alternans and the age at diagnosis. The sinus heart rate measured from a 24 h electrocardiograph was abnormally low (< 50 min) in three patients (1, 4 and 5 years old) and did not increase sufficiently with the administration of atropine in five of the six patients with congenital long QT syndrome. From intracardiac electrophysiological studies, the corrected sinus node recovery time was prolonged in three patients and the total sinoatrial conduction time was prolonged in two patients. In most patients who had an abnormally long sinoatrial conduction time and corrected sinus node recovery time, these values returned to normal following atropine administration. In one patient, the corrected sinus node recovery time was prolonged paradoxically by atropine. Sinus node dysfunction in congenital long QT syndrome was affected by vagotony associated with a right sympathetic nerve system abnormality.     

MATERNAL HYPERTHYROIDISM AND CONGENITAL MALFORMATION IN THE OFFSPRING

Six hundred and forty-three neonates from mothers with Graves' disease were examined for major malformations of external organs to compare the influence of maternal hyperthyroidism vs. ingestion of methimazole (MMI) during the first trimester on the incidence of congenital malformations. The subjects were divided into four groups according to maternal therapy and thyroid status during the first trimester as follows: (1) infants whose mothers did not receive MMI and were hyperthyroid (Group 1), (2) infants whose mothers did not receive MMI and were euthyroid (Group 2), (3) infants whose mothers received MMI and were hyperthyroid (Group 3) and (4) infants whose mothers received MMI and were euthyroid (Group 4). The prevalence of malformed infants in these four groups was 6.0% (three of 50), 0.3% (one of 350), 1.7% (two of 117) and 0.0% (none of 126), respectively. The incidence in Group 1 was significantly higher than that in Group 2 (P less than 0.01). There was no discernible dose dependency of MMI on the occurrence of malformations. These findings suggest that maternal uncontrolled hyperthyroidism may cause congenital malformations and that the beneficial role of MMI treatment outweighs its teratogenic effect, if any.     

Influence of piecemeal necrosis on the compensatory increase of mitochondrial respiratory enzymes of the tumour-bearing liver: Clinical study of 53 surgical cases

The relationships between histological findings, adaptively increased cytochrome a(+a3) levels in chronic liver disease and complications after hepatectomy were studied in order to clarify the mechanism of mitochondrial derangement. The liver specimens of 53 hepatectomized patients were randomly evaluated by three independent hepatopathologists and were compared with cytochrome a(+a3) levels in the biopsied liver, the extent of operation and postoperative complications. The cytochrome a(+a3) concentrations did not show any significant difference between cases of chronic hepatitis and liver cirrhosis nor groups classified by regeneration. Severity of piecemeal necrosis was categorized into three groups: group A--minimal (n = 20); group B--moderate (n = 19); and group C--severe (n = 14). There were significant differences (P less than 0.01) in cytochrome a(+a3) concentrations between the groups (A: 99 +/- 9; B: 135 +/- 6; C: 155 +/- 10 pmol/mg of mitochondrial protein). Extensive hepatectomy, involving segmentectomy or more, was frequently complicated (four of nine, 44.4%) in group C, whereas there were few complications (two of 16, 12.5%) in group A cases in which extensive hepatectomy was performed. Evidence will be presented which will show that deranged liver function, as indicated by cytochrome a(+a3) levels, is closely correlated with piecemeal necrosis. This may be attributed to the damage of periportal hepatocytes which are the main sites of oxidative phosphorylation.     

Synthesis of human angiotensinogen (1-17) containing one of the putative glycosylation binding sites and its hydrolysis by human renin and porcine pepsin

The N-terminal heptadecapeptide of human angiotensinogen (Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-His-Asn-Glu-Ser-Thr-NH₂), with the C-terminal carboxyl group amidated, was synthesized in order to study the role of Asn-Glu-Ser, a putative carbohydrate binding site, on the hydrolysis by human renin. The synthesis was performed by fragment condensation using the Honzl and Rudinger azide procedure. In our conditions for azide segment condensation, histidine racemization was demonstrated to be negligible for most of the condensation reactions. Human renin liberates angiotensin I from h-angiotensinogen (1-17)-NH₂ with a K_m value of 3.4 × 10^?5m , at pH 7.3 and 37° being similar to h-angiotensinogen (1-13), an analog without the carbohydrate binding site. However, the V_max value of 4.1 × 10^?9mol/G.U. min is one order of magnitude higher. Porcine pepsin was demonstrated to cleave preferentially Leu¹⁰-Val¹¹ bond and, surprisingly, His⁹-Leu¹⁰ as well.     

Randomized Trial Comparing Chemotherapy Alone and Chemotherapy Plus Chest Irradiation in Limited Stage Small Cell Lung Cancer: A Preliminary Report

In order to assess the effectiveness of chest irradiation inaddition to intensive chemotherapy in limited stage small celllung cancer, 50 patients were randomized to receive either chemotherapyalone or chemotherapy plus chest irradiation, between April1981 and October 1985. The chemotherapy regimen consisted ofa four-drug combination of cyclophosphamide, vincristine, methotrexate,and procarbazine, and a three-drug combination of etoposide,adriamycin, and nimustine, given alternately every 8 weeks.One group of 26 patients received the chemotherapy alone, andanother group of 24 patients received chest irradiation with40 Gy between cycles 1 and 2 of the chemotherapy. Complete responserates were quite similar in the two groups; 50% for those receivingchemotherapy alone, and 59% for those receiving chemotherapyplus chest irradiation. There were no significant differencesin median survival (15 months versus 12 months) and in long-termsurvival rates between the two groups with a median follow-upperiod of 26 months. The combined modality treat ment was moretoxic than chemotherapy aIone two patients receiving such treatmentdied of radiation pneumonitis. It is concluded that chest irradiationcombined with chemotherapy does not affect the response rate,survival, or pattern of recurrence in patients with limitedstage small cell lung cancer.     

Solitary psoas muscle metastasis after radical nephrectomy for renal cell carcinoma

Skeletal muscle is a very rare location for the metastasis of renal cell carcinoma (RCC) and only one case of solitary metastasis to the psoas muscle has been reported. We present a 63-year-old male patient with late recurrence (14 years) after left side radical nephrectomy for RCC. He first visited Chikushi Hospital, Fukuoka University, Japan in January 2000 for a postoperative follow-up because he had shifted residence to the area. Follow-up was by abdominal computed tomography (CT) and chest X-ray. In December 2001, a CT scan showed a 1.5 cm enhanced mass in the right psoas muscle without any other metastasis. The mass was resected that month and histological study showed RCC metastasis.